Odorant identity is encoded in the spatial distribution of activity across olfactory bulb (OB) glomeruli. Glomeruli are the fundamental computational elements in the bulb, with each glomerulus receiving feed- forward input from a single class of olfactory receptor neurons. However, the patterns of activation for specific stimuli, i.e. odor maps, can be dramatically altered by the bulb's intrinsic circuitry. For example, it has been shown that the spiking activity of the OB projection neurons, mitral and tufted (MT) cells, does not correspond directly to local glomerular activation. One critical, unresolved question in the olfactory system is how the bulb's intrinsic circuitry refines odor maps into the stimulus representation that is eventually transmitted to the olfactory cortices. The goal of this proposal is to elucidate the intrinsic circuit organizations and mechanisms responsible for shaping the OB's spatial representation of odorants. Lateral inhibition (LI) is believed to play a key role in this process. LI is the capacity of two or more neuronal pools to exhibit mutual inhibition. There are two predominant models of lateral inhibition in the bulb. Some recent studies have suggested that LI in the bulb is organized in a center-surround fashion, while others have argued that LI in the OB is distance-independent and follows a sparse network organization. An additional complexity is that LI in the bulb exhibits complex temporal dynamics and can be modulated by respiration. However, to date, neither the functional organization of these inhibitory circuits or their temporal modulation by respiration has been investigated in vivo. In order to understand the circuit mechanisms underlying sensory perception of the odor maps, both the organization and modulation of LI in the OB need to be determined. This proposal aims to characterize LI in the OB by focusing on two parameters: distance and respiratory phase. The results from the distance studies will elucidate the spatial organization of lateral inhibition in the bulb and explore the possibility of a center-surround inhibitory network as a basis for odor map processing. Studies of respiratory phase modulation will have important implications for the processing of retronasal smells in the sensation of flavor. Retronasal processing occurs when volatiles in the mouth activate the olfactory pathway during expiration. These studies will provide the first functional evidence for respiration phase-dependent enhancement of retronasal processing as a basis for the perception of flavor. Taken together, the results from the proposed studies will advance our understanding of how odor maps are processed and modulated by the OB network. PUBLIC HEALTH RELEVANCE: This project proposes to elucidate the organization and circuit mechanisms involved in processing and perceiving olfactory stimuli in the olfactory bulb (OB). Processing in the OB plays an important role in many human diseases including obesity and anosmia (inability to smell) - the OB is also one of the first brain regions to show indications of Alzheimer's and Parkinson's diseases. A more thorough knowledge of the functional organization and circuit mechanisms of the OB will form a foundation to understand the olfactory components of these diseases. The relevance of these studies falls within the priority areas in the "Healthy People 2010" objectives, specifically objective ENT_VLS HP2020-18.